Evidence for a novel gene associated with human influenza A viruses
Date
2009-11-16
Authors
Clifford, Monica
Twigg, James
Upton, Christopher
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Influenza A virus genomes are comprised of 8 negative strand single-stranded RNA
segments and are thought to encode 11 proteins, which are all translated from mRNAs
complementary to the genomic strands. Although human, swine and avian influenza A viruses are
very similar, cross-species infections are usually limited. However, antigenic differences are
considerable and when viruses become established in a different host or if novel viruses are created
by re-assortment devastating pandemics may arise.
Results: Examination of influenza A virus genomes from the early 20th Century revealed the
association of a 167 codon ORF encoded by the genomic strand of segment 8 with human isolates.
Close to the timing of the 1948 pseudopandemic, a mutation occurred that resulted in the extension
of this ORF to 216 codons. Since 1948, this ORF has been almost totally maintained in human
influenza A viruses suggesting a selectable biological function. The discovery of cytotoxic T cells
responding to an epitope encoded by this ORF suggests that it is translated into protein. Evidence
of several other non-traditionally translated polypeptides in influenza A virus support the translation
of this genomic strand ORF. The gene product is predicted to have a signal sequence and two
transmembrane domains.
Conclusion: We hypothesize that the genomic strand of segment 8 of encodes a novel influenza
A virus protein. The persistence and conservation of this genomic strand ORF for almost a century
in human influenza A viruses provides strong evidence that it is translated into a polypeptide that
enhances viral fitness in the human host. This has important consequences for the interpretation
of experiments that utilize mutations in the NS1 and NEP genes of segment 8 and also for the
consideration of events that may alter the spread and/or pathogenesis of swine and avian influenza
A viruses in the human population.
Description
BioMed Central
Keywords
Citation
Clifford et al. Evidence for a novel gene associated with human influenza A viruses.Virology Journal 2009 6:198